Alterations of human lipid profile and mitochondrial DNA copy number induced by PPD exposure

As a class of industrial antioxidants, N, N'-substituted p-phenylenediamines (PPDs) find extensive application in rubber product stabilization, leading to significant human exposure and various toxic implications. Whether human exposure to PPDs can affect the human lipid metabolism remains unclear. This study investigated the associations between human urinary PPD concentrations and serum lipid profiles or mitochondrial DNA copy number (mtDNAcn) in a cohort of 265 Chinese adults. Six PPDs were frequently measurable in human urine, with N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD; mean 2.08 ng/mL), N, N'-di-2-naphthyl-p-phenylenediamine (DNPD; 1.37 ng/mL), and N-phenyl-N'-cyclohexyl-p-phenylenediamine (CPPD; 1.04 ng/mL) being the dominant compounds. Results revealed significant (p < 0.05) positive associations between human 6PPD, CPPD, and N-isopropyl-N'-phenyl-1,4-phenylenediamine (IPPD) exposure and elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol levels. Mixed human PPD exposure, assessed using weighted quantile sum and Bayesian kernel machine regression models, further highlighted 6PPD as the primary contributor to lipid dysregulation. These findings underscore the potential cardiovascular disease risks of human exposure to PPDs, and emphasize the need for further research into their other metabolic impacts in humans.